APOE and Alzheimer disease: For example, we know that up to 36.1% of APOE ε4 allele non-carriers clinically diagnosed with Alzheimer’s Dementia do not have Alzheimer’s pathology as measured by PIB-PET.[9] GWAS studies that utilize PET amyloid signal or a CSF biosignture as quantitative endophenotype offer an opportunity, in principle, to define more objective phenotype, and establish direct associations between genetic variations, disease state biomarkers and disease progression.